Elevated matrix metalloproteinase-2 and -3 production from human diabetic dermal fibroblasts

Br J Dermatol. 2003 Jul;149(1):13-6. doi: 10.1046/j.1365-2133.2003.05262.x.

Abstract

Background: Diabetic foot ulcers are characterized by elevated levels of matrix metalloproteinases (MMP), which could lead to excessive matrix breakdown and disruption to healing. It is unknown if this elevation is a function of wound healing, or if it is present within normal skin and a primary contributor to the increased risk of impaired healing.

Objectives: To determine whether diabetic fibroblasts from unwounded skin show elevated MMP production compared with their nondiabetic counterparts.

Patients and methods: Circular skin biopsies (4 mm diameter) were taken from the inside upper arm of four controls without diabetes and from four subjects with insulin-treated diabetes. Fibroblasts were incubated for a further 72 h and conditioned medium was collected and stored at -20 degrees C. The conditioned medium was assessed by gelatin zymography and Western blotting for MMP-2 and MMP-3.

Results: Diabetic dermal fibroblasts showed significantly elevated production of MMP-2 (P < 0.05) and pro-MMP-3 (P < 0.05) when compared with their nondiabetic counterparts.

Conclusions: Dermal fibroblasts from normal unwounded skin are characterized by increased MMP production and this may be a primary contributing factor to the increased risk of nonhealing foot ulceration in diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Culture Media, Conditioned
  • Diabetes Mellitus / enzymology*
  • Female
  • Fibroblasts / enzymology*
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 3 / biosynthesis*
  • Middle Aged
  • Skin / enzymology*
  • Wound Healing

Substances

  • Culture Media, Conditioned
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 2